NEUROCHEMICAL MECHANISMS OF EXPERIMENTAL CONCUSSION

我们的目标是开发一种药物治疗方案，用于治疗确诊的 头部受伤。具体地说，我们将研究胆碱能 液体所致神经功能障碍的特定脑区神经元 大鼠敲击伤模型。据推测，中国的增长 紧接头部后某些脑区的胆碱能活动 损伤可能会导致急性和更持久的神经缺陷。这个 急性和更持久的神经缺陷的机制可能非常 不同；一些更长期的赤字可能反映了减少 后期部分脑区的胆碱能活动。中的更改 胆碱能神经化学将与选定的神经疾病相关 头部损伤后不同时间的缺陷。与以前的经验一样 已经表明东莨菪碱预处理可以减少神经功能缺陷。 在头部损伤后，将在以下时间测量东莨菪碱的作用 受伤后选择的时间。将进行实验，以 确定是否有一个限定的时间段，在这段时间内必须使用东莨菪碱。 用来减少持续性的神经缺陷。特定的 中枢胆碱能神经元的操作将被用来证实 东莨菪碱对神经转归的作用机制。中环 脑内注射可增强或降低胆碱能张力 分别为二异丙基氟磷酸盐(DFP)或半氯-3。急性 神经学测试将包括测量简单反射(耳廓、角膜 和惊恐反射)以及姿势和伤害性躯体运动功能 (翻正和逃逸反应、肌肉张力、运动活动和爪子 和尾部屈曲反射)。将对慢性神经缺陷进行评估 通过测量在横梁上保持平衡的能力和习得的回避任务 需要协调运动(横梁行走)。中枢性胆碱能 活性将通过量化组织中的乙酰胆碱周转率来评估 通过大量碎片成像技术对特定的大脑区域进行击打 从输液中测量相对掺入的氚标记 磷酰胆碱前体转化为胆碱和乙酰胆碱。乙酰胆碱 周转率将在以下区域进行测量：桥背内侧 被盖、桥背外侧被盖/臂旁核、乳头状核 和下丘脑的后核，丘脑延髓间核， 杏仁核、丘脑前腹核、海马体 纹状体、前额叶皮质和顶叶皮质。

Our goal is to develop a pharmacological treatment regimen for conclusive head injury. Specifically, we will investigate the role of cholinergic neurons in specific brain areas in neurological deficits following fluid percussion injury in the rat. It is postulated that increases in cholinergic activity in certain brain areas immediately following head injury may lead to acute and longer lasting neurologic deficits. The mechanisms of acute and longer lasting neurological deficits may be very different; some of the more chronic deficits may reflect decreased cholinergic activity in some brain regions at the later times. Changes in cholinergic neurochemistry will be correlated with selected neurological deficits at various times following head injury. As previous experience has shown that scopolamine pretreatment reduces the neurological deficits following head injury, the actions of scopolamine will be measured at selected times following injury. Experiments will be performed to determine if there is a restricted time period in which scopolamine must be administered to reduce persistent neurological deficits. Specific manipulations of central cholinergic neurons will be used to confirm the mechanism of action of scopolamine on neurological outcome. Central cholinergic tone will be enhanced or decreased by intracerebral injection of diisopropylfluorophosphate (DFP) or hemicholium-3, respectively. Acute neurological testing will include measuring simple reflexes (pinna, corneal and startle reflexes) and postural and nociceptive somatomotor function (righting and escape responses, muscle tone, locomotor activity, and paw and tail flexion reflexes). Chronic neurological deficits will be assessed by measuring ability to to balance on a beam and a learned avoidance task requiring coordinated movement (beam-walking). Central cholinergic activity will be assessed by quantitating acetylcholine turnover in tissue punches of specific brain regions by a mass fragmentographic technique that measures the relative incorporation of deuterium label from infused phosphorylcholine precursor into choline and acetylcholine. Acetylcholine turnover will be measured in the following areas: dorsomedial pontine tegmentum, laterodorsal pontine tegmentum/parabrachial nucleus, mammillary and posterior nuclei of the hypothalamus, interpenducular nucleus, amygdala, anteroventral nucleus of the thalamus, hippocampus, corpus striatum, prefrontal cortex and parietal cortex.